Safety and Efficacy of KRT-232 in Combination With Acalabrutinib in Subjects With R/R DLBCL or R/R CLL

NCT04502394 | Unknown Phase 1 FDA Drug

• 1 other identifier: KRT-232-111
• Study Type: interventional
• Target: 84
• Locations: 11 countries
• Sites: 45

Brief Summary

This study evaluates KRT-232, a novel oral small molecule inhibitor of MDM2, combined with acalabrutinib for the treatment of adults with Diffuse Large B-Cell Lymphoma and Chronic Lymphocytic Leukemia. Participants must be relapsed/refractory (having failed prior therapy)

Conditions

Diffuse Large B Cell Lymphoma; Chronic Lymphocytic Leukemia; Non Hodgkin Lymphoma

Keywords

navtemadlin

Outcome Measures

Primary Outcomes (3)

• Primary Objective Phase 1b:To determine the KRT-232 maximum tolerated dose/ maximum administered dose (MTD/MAD) and recommended Phase 2 Dose (RP2D) in combination with acalabrutinib in subjects with R/R DLBCL or R/R CLL

  Endpoint/Outcome Measures: Dose-limiting toxicities will be used to establish the MTD/MAD of KRT-232 in combination with acalabrutinib. The Safety Review Committee will determine the RP2D based on safety data of the combination of KRT-232 and acalabrutinib.

  56 Days

• Primary Objective Phase 2: Cohort 1: To determine the complete response (CR)

  Endpoint/Outcome Measures: Cohort 1: The proportion of subjects with CR as assessed by investigators per the Lugano Classification.

  1 Year

• Primary Objective Phase 2: Cohort 2: To determine the rate of CR/complete remission with incomplete hematologic recovery (CRi) rate in R/R CLL

  Endpoint/Outcome Measures: Cohort 2: The proportion of subjects with CR/CRi as assessed by investigators per iwCLL Response Criteria.

  1 Year

Secondary Outcomes (7)

• Phase 1b Secondary Objective: Pharmacokinetic (PK) profile

  Baseline, 1, 2, 4, 6 and 24 hours post dose on days 1 and 2 of cycle 1 (each cycle is 28 days); Baseline and 2 hours post dose on day 1 and 24 hours post dose on day 8 of cycle 2

• Phase 1b Secondary Objective: Pharmacokinetic (PK) profile

  Baseline, 1, 2, 4, 6 and 24 hours post dose on days 1 and 2 of cycle 1 (each cycle is 28 days); Baseline and 2 hours post dose on day 1 and 24 hours post dose on day 8 of cycle 2

• Phase 1b Secondary Objective: Pharmacokinetic (PK) profile

  Baseline, 1, 2, 4, 6 and 24 hours post dose on days 1 and 2 of cycle 1 (each cycle is 28 days); Baseline and 2 hours post dose on day 1 and 24 hours post dose on day 8 of cycle 2

• Phase 1b Secondary Objective: Pharmacokinetic (PK) profile

  Baseline, 1, 2, 4, 6 and 24 hours post dose on days 1 and 2 of cycle 1 (each cycle is 28 days); Baseline and 2 hours post dose on day 1 and 24 hours post dose on day 8 of cycle 2

• Phase 1b Secondary Objective: Pharmacokinetic (PK) profile

  Baseline, 1, 2, 4, 6 and 24 hours post dose on days 1 and 2 of cycle 1 (each cycle is 28 days); Baseline and 2 hours post dose on day 1 and 24 hours post dose on day 8 of cycle 2

Study Arms (2)

Cohort 1 (R/R DLBCL)

EXPERIMENTAL

KRT-232 will be administered orally, once daily (QD), on days 1-7 in a 28-day cycle. Acalabrutinib at 100 mg twice a day (BID) continuously starting on Day 1 in a 28-day cycle.

Drug: KRT-232; Drug: acalabrutinib

Cohort 2 (R/R CLL)

EXPERIMENTAL

KRT-232 will be administered orally, once daily (QD), on days 1-7 in a 28-day cycle. Acalabrutinib at 100 mg twice a day (BID) continuously starting on Day 1 in a 28-day cycle.

Drug: KRT-232; Drug: acalabrutinib

Interventions

KRT-232 DRUG

KRT-232 is an experimental MDM2 inhibitor anticancer drug taken by mouth

Cohort 1 (R/R DLBCL); Cohort 2 (R/R CLL)

acalabrutinib DRUG

acalabrutinib is a BTK inhibitor anticancer drug taken by mouth

Also known as: ACP-196

Cohort 1 (R/R DLBCL); Cohort 2 (R/R CLL)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Cohort 1: Confirmed diagnosis of TP53wt DLBCL (WHO); R/R DLBCL after at least 2 prior lines of treatment or 1 prior for patients who are ineligible for stem cell transplant
• Cohort 2: Confirmed diagnosis of TP53wt CLL (iwCLL); R/R CLL after at least 1 prior line of treatment
• ECOG 0 to 2
• Adequate hematologic, hepatic, and renal functions.

You may not qualify if:

• Prior treatment with any MDM2 inhibitor
• Prior treatment with any BTK inhibitor

Sponsors & Collaborators

• Kartos Therapeutics, Inc.: lead

Study Sites (45)

Goshen Center for Cancer Care

Goshen, Indiana, 46526, United States

RECRUITING

University of Cincinnati

Cincinnati, Ohio, 45221, United States

RECRUITING

The Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

RECRUITING

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

RECRUITING

Royal Adelaide Hospital

Adelaide, Australia

RECRUITING

Eastern Health - Box Hill Hospital

Box Hill, Australia

RECRUITING

Barwon Health

Geelong, Australia

RECRUITING

Royal Perth Hospital

Perth, Australia

RECRUITING

Antwerp University Hospital (UZA)

Edegem, Belgium

RECRUITING

Jessa Ziekenhuis

Hasselt, Belgium

RECRUITING

University Hospital (UZ) Leuven

Leuven, Belgium

RECRUITING

Fakultni Nemocnice Hradec Kralove

Nový Hradec Králové, Czechia

RECRUITING

Fakultni nemocnice Ostrava

Ostrava, Czechia

RECRUITING

Vseobecna fakultni nemocnice v Praze

Prague, Czechia

RECRUITING

CHU de Nantes - Hôtel-Dieu

Nantes, France

RECRUITING

Centre Henri Becquerel

Rouen, France

RECRUITING

CHRU de Tours - Hôpital Bretonneau

Tours, France

RECRUITING

Centro Riferimento Oncologico - Aviano

Aviano, Italy

RECRUITING

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori

Meldola, Italy

RECRUITING

ASST Grande Ospedale Metropolitano Niguarda

Milan, Italy

RECRUITING

IRCCS Ospedale San Raffaele

Milan, Italy

RECRUITING

Fondazione IRCCS Policlinico San Matteo

Pavia, Italy

RECRUITING

Centro Ricerche Cliniche di Verona s.r.l.

Verona, Italy

RECRUITING

Copernicus PL Sp. z o.o., Wojewodzkie Centrum Onkologii

Gdansk, Poland

RECRUITING

Uniwersyteckie Centrum Kliniczne, Klinika Hematologii i Transplantologii

Gdansk, Poland

RECRUITING

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy, Oddzial w Gliwicach - Klinika Transplantacji Szpiku i Onkohematologii

Gliwice, Poland

RECRUITING

Pratia MCM Krakow

Krakow, Poland

RECRUITING

Szpital Uniwersytecki Krakow - Oddzial Kliniczny Hematologii

Krakow, Poland

RECRUITING

Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego we Wroclawiu

Wroclaw, Poland

RECRUITING

Hospital de Braga

Braga, Portugal

RECRUITING

Centro Hospitalar Universitario de Lisboa Norte - Hospital de Santa Maria

Lisbon, Portugal

RECRUITING

Champalimaud Cancer Center

Lisbon, Portugal

RECRUITING

Instituto Portugues de Oncologia do Porto Francisco Gentil, EPE

Porto, Portugal

RECRUITING

Centro Hospitalar de Vila Nova de Gaia/Espinho EPE

Vila Nova de Gaia, Portugal

RECRUITING

National Cancer Center

Goyang, South Korea

RECRUITING

Gachon University Gil Medical Center

Incheon, South Korea

RECRUITING

Samsung Medical Center

Seoul, South Korea

RECRUITING

Seoul National University Hospital

Seoul, South Korea

RECRUITING

Seoul St. Mary's Hospital

Seoul, South Korea

RECRUITING

Severance Hospital, Yonsei University Health System

Seoul, South Korea

RECRUITING

Kantonsspital St. Gallen

Sankt Gallen, Switzerland

RECRUITING

St James's University Hospital

Leeds, United Kingdom

RECRUITING

King's College Hospital

London, United Kingdom

RECRUITING

Royal Marsden Foundation Trust

London, United Kingdom

RECRUITING

University Hospital Southampton NHS Foundation Trust

Southampton, United Kingdom

RECRUITING

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Non-Hodgkin

Interventions

navtemadlin; 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-(isopropylsulfonyl)-3-methylbutan-2-yl)-3-methyl-2-oxopiperidin-3-yl)acetic acid; acalabrutinib

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Hematologic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

John Mei

CONTACT

650-542-0136; jmei@kartosthera.com

Michael Yee

CONTACT

650-839-7361; myee@kartosthera.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: An Open-label, Phase 1b/2 Study of KRT-232 in combination with acalabrutinib in Subjects with B-cell Non-Hodgkin Lymphoma

Study Record Dates

• First Submitted: July 27, 2020
• First Posted: August 6, 2020
• Study Start: February 23, 2021
• Primary Completion: October 1, 2022
• Study Completion: March 1, 2024
• Last Updated: August 4, 2022

Record last verified: 2022-08

Locations

PT (5); KR (6); GB (4); CH (1); US (4); BE (3); AU (4); CZ (3); FR (3); IT (6); PL (6)